Enterocyte-like differentiation of the Caco-2 intestinal cell line is associated with increases in AP-1 protein binding

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The nuclear factor AP-1, a large family of transcription factors composed of the Jun and Fos protein families, plays a role in the differentiation of various cells; the role of the AP-1 factors in intestinal differentiation is not known. Members of the AP-1 family can be activated by the Ras pathway and, in addition, Ras appears to be important for gut differentiation. The purpose of this study was to determine whether AP-1 activity is altered in the Caco-2 cell line, which spontaneously differentiates to a small bowel phenotype after confluency, and the Caco-2- ras cell line, which exhibits differentiated properties regardless of culture conditions. AP-1 binding activity, consisting of c-Jun, JunD, c-Fos and Fra-2 proteins, was increased in Caco-2 cells at 3 days postconfluency, a time point associated with G 1 block and cessation of proliferation. Steady state levels of JunD were increased at day 3 postconfluency as determined by Western blot. Furthermore, AP-1 binding was increased in preconfluent Caco-2- ras cells compared with parental Caco-2 cells, suggesting that AP-1 induction may be mediated by the Ras pathway. The early induction of AP-1 binding activity suggests a role for these proteins in the differentiation of the Caco-2 intestinal cell line.